Exploring the impact of baseline and on-treatment variables on durability of responses to fostemsavir through weeks 96 and 192 in the phase 3 BRIGHTE study.

OBJECTIVES

The gp120-directed attachment inhibitor fostemsavir was effective in people with multidrug-resistant (MDR) HIV-1 in the BRIGHTE study. Understanding factors associated with virologic response can help clinicians optimize treatment and identify individuals for fostemsavir-based regimens. In previous multivariable analyses, baseline CD4+ T-cell count, baseline log10 HIV-1 RNA and temsavir plasma concentration were associated with virologic response through 24 weeks. This expanded analysis evaluated predictors of the durability of response at Weeks 96 and 192.

METHODS

BRIGHTE participant data (Randomized Cohort [RC], n = 272; Non-randomized Cohort, n = 99) were evaluated to examine baseline factors associated with virologic outcomes (HIV-1 RNA <40 copies/mL [Snapshot]; protocol-defined virologic failure [PDVF]) using linear/logistic regression with stepwise selection. A separate analysis evaluated baseline factors for association with treatment-adherent PDVF.

RESULTS

In RC participants, higher baseline log10 HIV-1 RNA, lower number of fully active available antiretrovirals in initial optimized background therapy (OBT) and a lower overall susceptibility score to newly used antiretrovirals in initial OBT were associated with lower odds of virologic response at Week 96. Baseline gp120 substitutions and dolutegravir use were additional factors through Week 192. Other baseline factors, including CD4+ T-cell count <20 cells/mm3, HIV-1 RNA ≥100 000 copies/mL, antiretroviral therapy duration >20 years or gp120 substitutions, had low predictive value for treatment-adherent PDVF in RC participants (Week 96, 35%; Week 192, 39%).

CONCLUSIONS

Multivariable analysis (MVA) identified several factors predictive of virologic response. No baseline factors were highly predictive of virologic failure at Weeks 96 or 192. Findings support the use of fostemsavir in diverse populations with MDR HIV-1.